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ADVANCES IN ANTIBIOTIC

THERAPY IN THE
CRITICALLY ILL
Seruni Allisa Aslim

PRESEPTOR:
Dr. Emilzon Taslim, Sp.An, KAO,KIC, M. Kes

Jean-Louis Vincent1*, Matteo Bassetti2, Bruno Franois3, George Karam4, Jean


Chastre5, Antoni Torres6, Jason A. Roberts7, Fabio S. Taccone1, Jordi Rello8, Thierry
Calandra9, Daniel De Backer10, Tobias Welte11 and Massimo Antonelli12
ABSTRACT
delayed
diagnosis,

occur frequently in
Challenging
critically ill patients
management
Infection

high prevalence of difficulties identifying


antibiotic-resistant strains causative microorganisms,
Abstract
Importance of early infection diagnosis
Antibiotic pharmacodynamics and
pharmacokinetics
Dosing decisions in different subgroups
of patients
Ventilator-associated pneumonia
The role of inhaled antibiotics
BACKGROUND

Intensive care unit (ICU) patients are likely to have or


develop infection

infection is a reason for admission

immunosuppression associated with critical illness

the large number of invasive devices used in these


patients
DIAGNOSIS

Diagnosis of infection in critically ill patients and identification of causative


microorganisms and their antIbiotic susceptibilities can be a challenge and yet early
Appropriate antibiotic therapy associated with improved outcomes accurate, rapid diagnosis is important

Typical clinical signs of infections are non-specific and can occur in many other
conditions in the critically ill population

C-reactive protein and procalcitonin (PCT) to rule out infection, none is specific
for infection

Diagnosis of infection still relies largely on culture-based techniques (several days)


in patients already receiving antibiotics, cultures may be negative

microbiological identification methods are being developed, including polymerase chain


reaction (PCR) and mass spectrometry with or without electrospray ionization
shorter times therapy, shorter lengths of hospital stay, and reduced hospital costs and likely to become
more widely used in the near future
ANTIBIOTIC THERAPY

EMPIRIC MANAGEMENT
combination versus monotherapy

COMBINATION
in vitro synergy between two drugs resulting in improved bacterial
killing
colistin glycopeptide (vancomycin or teicoplanin) combination was
shown in vitro to be synergistic against multidrug- resistant (MDR)
Gram-negative bacteria, especially Acine- tobacter baumanni
may provide a greater overall spectrum of activity
increased drug toxicity
Risk of super- infection with resistant bacteria or fungal infections
increased cost
COMBINATION
In a cohort of patients with septic shock, combination therapy of a -
lactam with other antibiotics was associated with a decrease in 28-day
mortality compared with -lactam monotherapy
in a prospective, combination therapy with macrolides was associated
with better outcomes compared with monotherapy in mechanically
ventilated patients with community-acquired pneumonia (CAP)
In a meta-regression analysis, combination therapy was consistently
associated with benefit in the more severely ill patients
In current guidelines, combination therapy is suggested for neutropenic
patients with sepsis, patients with infec- tions caused by MDR
pathogens and patients with severe respiratory infections and septic
shock
DE-ESCALATION?

Decisions regarding empiric antibiotic therapy are based on


two approaches:

a judgment that the likely agent has normal antibiotic susceptibility and
can therefore be treated as such with possible need for escalation to
second-line drugs after microbiological identification

a judgment, based on local microbiology patterns and clinical presentation,


that the infecting microorgan- ism may be MDR and should be treated as
such, with possible de-escalation to a simpler antibiotic regimen after
identification and antibiotic susceptibilities of the causative microorganism
are known
WHEN TO STOP?

Decisions about duration of


antibiotic therapy need to be
individualized, taking into
Current guidelines account different variables
regarding the patient (e.g.,
advise a 710 day severity of illness, clinical re-
course, unless poor sponse), the type of infection
(e.g., source control, deep-
prognosis predictors seated infection [e.g., bone
are present infection], MDR pathogens) and
the availability of diagnostic
tools (e.g., clinical/ laboratory
scores, biomarker)
DOSING ISSUES

Pharmacokinetics/pharmacodynamics Target site penetration

Clearance Volume of distribution


Doses of -lactams

Doses of aminoglycosides

Dosing in obese patients

Dosing during extracorporeal therapies


A SPECIAL SITUATION: VAP

VAP is the leading cause of nosocomial


infection in the ICU and a risk factor for
increased mortality.
A PLACE FOR NEBULIZED ANTIBIOTICS IN
VAP?
For patients receiving mechanical ventilation, aerosolized
antibiotics delivered via an ef ficient system may achieve
airway -drug concentrations 100 300-fold higher than the MIC
of most bacteria, including MDR pathogens, with reduced
systemic toxicity and reduced pressure for selec - tion of
resistant organisms

Several antibiotics have been studied as aerosolized agents;


however, how their dosing should be adjusted for optimal
ef ficacy and safety remains unclear
NEW ANTIBIOTICS IN THE PIPELINE

very few new


antibiotics have
been developed over
the past 10 years
but there are some
promising agents in
the pipeline.
NON-ANTIBIOTIC, ADJUNCTIVE THERAPIES

toxin-neutralizing antibodies
Fecal flora reconstitution by
fecal transplantation
oligofructose prebiotics

Monoclonal antibodies
CONCLUSIONS

Management of infection in critically ill patients is an evolving


challenge, in part because of the ever -present threat of MDR
strains. Alterations in PK/PD parameters in critically ill patients
can complicate dosing issues, yet adequate antibiotic treatment
is crucial to optimize survival rates.
CONCLUSIONS

Therapeutic drug monitoring is likely to be more


widely used in the future.

Antibiotic choices and durations need to be


individualized for each patient according to specific
patient characteristics, disease severity, likely
infecting organisms, and local resistance patterns.
CONCLUSIONS

Although more responsible antibiotic


prescribing may help reduce antibiotic
pressure and development of antibiotic
resistance, research needs to continue to try
and identify new antibiotics and adjunctive
therapies.